The COVID-19 pandemic perturbed air pollutant emissions as cities shutdown worldwide. Peroxyacyl nitrates (PANs) are important tracers of photochemistry that are formed through the oxidation of non-methane volatile organic compounds (NMVOCs) in the presence of nitrogen oxide radicals (NOx = NO + NO2). We use satellite measurements of free tropospheric PANs from the S-NPP Cross-Track Infrared Sounder (CrIS) over eight of the world’s megacities: Mexico City, Beijing, Los Angeles, Tokyo, São Paulo, Delhi, Lagos, and Karachi. We quantify the seasonal cycle of PANs over these megacities and find seasonal maxima in PANs correspond to seasonal peaks in local photochemistry. CrIS is used to explore changes in PANs in response to the COVID-19 lockdowns. Statistically significant changes to PANs occurred over two megacities: Los Angeles (PAN decreased) and Beijing (PAN increased). Our analysis suggests that large perturbations in NOx may not result in significant declines in NOx export potential of megacities.